Mixed features: evolution of the concept, past and current definitions, and future prospects

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Alan C. Swann

Mixed states address the relationships between episodes and the course of an illness, presenting significant clinical challenges. Recurrent affective disorders were described thousands of years ago as dimensional disturbances of the basic elements of behavior, combining the characteristics of what we would now consider manic and depressive episodes. It was recognized from the beginning that combinations of depressive and manic features are associated with a severe illness course, including increased suicide risk. Early descriptions of affective disorders formulated them as systemic illnesses, a concept supported by more recent data. Descriptions of affective disorders and their course, including mixed states, became more systematic during the 19th century. Structured criteria achieved importance with evidence that, in addition to early onset, frequent recurrence, and comorbid problems, mixed states had worse treatment outcomes than other episodes. In contrast to 2000 years of literature on recurrent affective episodes and mixed states, the unipolar–bipolar disorder distinction was formalized in the mid-20th century. Mixed-state criteria, initially developed for bipolar disorder, ranged from fully combined depression and mania to the DSM–5 criteria, no longer limited to bipolar disorder, of a primary depressive or manic episode with at least three symptoms of the other episode type. The challenges involved in understanding and identifying mixed states center largely on what drives them, including (1) their formulation as either categorical or dimensional constructs, (2) the specificity of their relationships to depressive or manic episodes, and (3) specificity for bipolar versus major depressive disorder. Their existence challenges the distinction between bipolar and major depressive disorders. The challenges involved in identifying the underlying physiological mechanisms go to the heart of these questions.

Author(s):  
Carol S. North ◽  
Sean H. Yutzy

Descriptions of mood disorders go back to the time of Hippocrates. Mood disorders are primarily characterized by depressed and/or elevated (manic) moods. The essential feature of mood disorders is an episode that is a distinct and persistent change from a person’s typical mood (depression or mania), accompanied by other depressive and manic symptoms, lasting 2 weeks for a major depressive episode and 1 week for a manic episode. Such episodes typically remit and recur over the course of time. Manic episodes define bipolar disorder. Severe depression without manic episodes is diagnosed as major depressive disorder. Mood disorders present a 10- to 30-fold risk for suicide. Effective treatments for mood disorders include medications, brain stimulation modalities, and psychotherapy.


2017 ◽  
Vol 41 (S1) ◽  
pp. S425-S425
Author(s):  
C. Novais ◽  
M. Marinho ◽  
M. Mota Oliveira ◽  
M. Bragança ◽  
A. Côrte-Real ◽  
...  

IntroductionEarly stages of bipolar disorder are sometimes misdiagnosed as depressive disorders. This symptomatology can lead to misinterpretation and under diagnosis of bipolar disorders.Objectives/aimsTo describe a patient with a new diagnosis of bipolar disorder after 23 years of psychiatric care.MethodsWe report a case of a 66-year-old man, with a previous psychiatric diagnosis of recurrent depressive disorder for the last 23 years, after a hospitalization in a psychiatric inpatient unit because of a major depressive episode. In subsequent years, he was regularly followed in psychiatric consultation with description of recurrent long periods of depressed mood requiring therapeutic setting, alternating with brief remarks of not valued slightly maladjusted behaviour. At 65, he came to the emergency room presenting with observable expansive and elevated mood, disinhibited behaviour, grandiose ideas and overspending, leading to his hospitalization with the diagnosis of a manic episode. In the inpatient unit care, we performed blood tests, cranial-computed tomography (CT) and a cognitive assessment. His medication has also been adjusted.ResultsLaboratory investigations were unremarkable. Cranial-CT showed some subcortical atrophy of frontotemporal predominance, without corroboration by the neuropsychological evaluation. The patient was posteriorly transferred to a residential unit for stabilization, where he evolved with major depressive symptoms that needed new therapeutic adjustment. Later he was discharged with the diagnosis of bipolar disorder.ConclusionsOur case elucidates the importance of ruling out bipolar disorder in patients presenting with depressive symptoms alternating with non-specific maladjusted behaviour, which sometimes can be a challenging task.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2016 ◽  
Vol 33 (S1) ◽  
pp. S493-S493
Author(s):  
J. Nogueira ◽  
R. Ribeiro ◽  
J. Vieira ◽  
R. Sousa ◽  
S. Mendes ◽  
...  

BackgroundThe corpus callosum (CC) is the largest white matter structure in the brain, which plays a crucial role in interhemispheric communication. Agenesis of the CC is a rare development anomaly, with unknown cause. It could be asymptomatic or associated with mental retardation and neurologic symptoms. Some case reports, post-mortem studies and image studies have linked thickness reduction and agenesis of CC with psychotic symptoms, mainly in schizophrenia patients. Lately, anatomical abnormalities in the CC have been reported in patients with Bipolar Disorder (BD).Case reportA 52-year-old woman was brought to the emergency room by the authorities after being physically aggressive to her 13-year-old daughter and inappropriate behavior in public. At the emergency department her mood was elevated with emotional lability, dispersible attention, slight increase of motor activity, pressured and difficult to interrupt speech, grandious and self-referent delusional ideas.Her past history revealed hippomaniac episodes characterized by periods of excessive shopping and hyperphagia. In 2008, she had a major depressive episode.Head CT-SCAN revealed agenesia of CC. She received the diagnosis of Manic Episode with mixed features and was treated with valproic acid, flurazepam and olanzapine.ConclusionThis case reinforces the fact that changes in CC, probably due to deficiency in myelination, could have a crucial importance in the pathophysiology of Bipolar Disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2021 ◽  
Author(s):  
Hong Wang ◽  
Yan-Xia Xiao ◽  
Jing-Ge Du ◽  
Xia Du ◽  
Lin Chen

Abstract Background: To investigate the clinical phenomenology and clinical features of the new concept of major depressive disorder and bipolar disorder depressive episodes with mixed features.Methods: A total of 357 patients with major depressive disorder or bipolar disorder depressive episodes were assessed, we compared the differences of clinical features with or without mixed features.Results: According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, the overall prevalence of mixed features was 9.52% (34/357) in major depressive disorder and bipolar disorder depressive episodes; specifically, the prevalence was 6.0% in major depressive disorder and 23.3% in bipolar disorder depressive episodes. Compared with the non-mixed features group, the mixed features group had more single individuals (P=0.002), earlier onset age (P=0.003), more patients with an onset age <25 years (P=0.001), and more previous incidences and prior hospitalizations (P<0.001, P=0.004, respectively), and fewer melancholic features (P=0.013).Logistic regression analysis showed that marital status (OR=0.237) and previous incidence (OR=1.478) was associated with mixed features.Conclusion: It indicates that previous incidence may be a risk factor of in patients with major depressive disorder and bipolar disorder depressive episodes with mixed features, and marital status may be a protective factor.


CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Minoru Takeshima

The DSM–5 incorporates a broad concept of mixed states and captured ≥3 nonoverlapping symptoms of the opposite polarity using a “with mixed features” specifier to be applied to manic/hypomanic and major depressive episodes. Pharmacotherapy of mixed states is challenging because of the necessity to treat both manic/hypomanic and depressive symptoms concurrently. High-potency antipsychotics used to treat manic symptoms and antidepressants can potentially deteriorate symptoms of the opposite polarity. This review aimed to provide a synthesis of the current evidence for pharmacotherapy of mixed states with an emphasis on mixed mania/hypomania. A PubMed search was conducted for randomized controlled trials (RCTs) that were at least moderately sized, included a placebo arm, and contained information on acute-phase and maintenance treatments of adult patients with mixed episodes or mania/hypomania with significant depressive symptoms. Most studies were post-hoc subgroup and pooled analyses of the data from RCTs for acute manic and mixed episodes of bipolar I disorder; only two prospectively examined efficacy for mixed mania/hypomania specifically. Aripiprazole, asenapine, carbamazepine, olanzapine, and ziprasidone showed the strongest evidence of efficacy in acute-phase treatment. Quetiapine and divalproex/valproate were also efficacious. Combination therapies with these atypical antipsychotics and mood stabilizers can be considered in severe cases. Olanzapine and quetiapine (alone or in combination with lithium/divalproex) showed the strongest evidence of efficacy in maintenance treatment. Lithium and lamotrigine may be beneficial given their preventive effects on suicide and depressive relapse. Further prospective studies primarily focusing on mixed states are needed.


CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Mark Zimmerman

During the past two decades, a number of studies have found that depressed patients frequently have manic symptoms intermixed with depressive symptoms. While the frequency of mixed syndromes are more common in bipolar than in unipolar depressives, mixed states are also common in patients with major depressive disorder. The admixture of symptoms may be evident when depressed patients present for treatment, or they may emerge during ongoing treatment. In some patients, treatment with antidepressant medication might precipitate the emergence of mixed states. It would therefore be useful to systematically inquire into the presence of manic/hypomanic symptoms in depressed patients. We can anticipate that increased attention will likely be given to mixed depression because of changes in the DSM–5. In the present article, I review instruments that have been utilized to assess the presence and severity of manic symptoms and therefore could be potentially used to identify the DSM–5 mixed-features specifier in depressed patients and to evaluate the course and outcome of treatment. In choosing which measure to use, clinicians and researchers should consider whether the measure assesses both depression and mania/hypomania, assesses all or only some of the DSM–5 criteria for the mixed-features specifier, or assesses manic/hypomanic symptoms that are not part of the DSM–5 definition. Feasibility, more so than reliability and validity, will likely determine whether these measures are incorporated into routine clinical practice.


CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 120-125 ◽  
Author(s):  
Gianni L. Faedda ◽  
Ciro Marangoni

The newly introduced Mixed Features Specifier of Major Depressive Episode and Disorder (MDE/MDD) is especially challenging in terms of pharmacological management. Prior to the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of the mixed features specifier were intradepressive hypomanic symptoms, always and only associated with bipolar disorder (BD).Intradepressive hypomanic symptoms, mostly referred to as depressive mixed states (DMX), have been poorly characterized, and their treatment offers significant challenges. To understand the diagnostic context of DMX, we trace the nosological changes and collocation of intradepressive hypomanic symptoms, and examine diagnostic and prognostic implications of such mixed features.One of the reasons so little is known about the treatment of DMX is that depressed patients with rapid cycling, substance abuse disorder, and suicidal ideation/attempts are routinely excluded from clinical trials of antidepressants. The exclusion of DMX patients from clinical trials has prevented an assessment of the safety and tolerability of short- and long-term use of antidepressants. Therefore, the generalization of data obtained in clinical trials for unipolar depression to patients with intradepressive hypomanic features is inappropriate and methodologically flawed.A selective review of the literature shows that antidepressants alone have limited efficacy in DMX, but they have the potential to induce, maintain, or worsen mixed features during depressive episodes in BD. On the other hand, preliminary evidence supports the effective use of some atypical antipsychotics in the treatment of DMX.


2021 ◽  
Author(s):  
Stephen M. Stahl

Long established as the preeminent source in its field, the eagerly anticipated fifth edition of Dr Stahl's essential textbook of psychopharmacology is here! With its use of icons and figures that form Dr Stahl's unique 'visual language', the book is the single most readable source of information on disease and drug mechanisms for all students and mental health professionals seeking to understand and utilize current therapeutics, and to anticipate the future for novel medications. Every aspect of the book has been updated, with the clarity of explanation that only Dr Stahl can bring. The new edition includes over 500 new or refreshed figures, an intuitive color scheme, fourteen new uses for older drugs and eighteen brand new drugs, coverage of Parkinson's Disease Psychosis, behavioural symptoms of dementia, and mixed features in major depressive episodes, and expanded information on the medical uses of cannabis and hallucinogen assisted psychotherapy.


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